TIMAR1: Targeted Imaging of Melanoma for Alpha-Particle Radiotherapy

• Sponsor: Viewpoint Molecular Targeting (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04904120
• Collaborator: Mayo Clinic (Other)
• Enrollment: 10
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 21.9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The study hypothesis is that new imaging agents [203Pb]VMT01 and [68Ga]VMT02 can be safely used in humans without independent biological effect and can be used to image melanoma tumors expressing the melanocortin sub-type 1 receptor (MC1R) by SPECT/CT and PET/CT imaging modalities respectively.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin); Melanoma Stage IV; Melanoma, Uveal; Melanoma, Mucosal	Drug: [203Pb]VMT01; Drug: [68Ga]VMT02	Phase 1

Detailed Description

This is a first-in-human study evaluating the suitability of [203Pb]VMT01 for SPECT/CT imaging and [68Ga]VMT02 for PET/CT imaging of MC1R-expressing metastatic melanoma. Study results will provide foundational data to develop imaging and dosing for future therapeutic trials of [212Pb]VMT01 for the treatment of metastatic melanoma.

The study will be a cross-over study with the participants serving as their own comparator. Participants with positive FDG-PET scans for stage IV (or inoperable stage III) metastatic melanoma will undergo SPECT/CT scans utilizing [203Pb]VMT01 followed a few weeks later by PET/CT scans utilizing [68Ga]VMT02, or vice versa. The order of the imaging agents will be randomly assigned.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: Archived tumor tissue will be tested for expression of the imaging target, melanocortin receptor sub-type 1 (MC1R). The qualified researcher who tests the sample, and the independent pathologist who reviews the results, will be blinded to a participant's identifying information and imaging results. Evaluators will not have access to the medical record. A pool of three qualified readers will evaluate study images (PET/CT and SPECT/CT). Images and medical information given to the readers will not include a participant's identifying information. The reader pool will not know the sequence of imaging for a participant or have access to the medical record. An independent medical physicist will validate imaging results and measurements of radiation absorbed and excreted by the participant's body. The physicist will be blinded to participant identifiers and demographics, as well as the sequence of imaging for a participant. The physicist will not have access to the medical record.
• Primary Purpose: Diagnostic
• Official Title: A Phase 1 Cross-over Biodistribution Study of [203Pb]VMT01 for Single Photon Emission Computed Tomography (SPECT) Imaging and [68Ga]VMT02 for Positron Emission Tomography (PET) Imaging of Stage IV Metastatic Melanoma
• Actual Study Start Date: Mar 5, 2021
• Anticipated Primary Completion Date: Oct 31, 2022
• Anticipated Study Completion Date: Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: [203Pb]VMT01 first Participants randomized to this arm will receive imaging agent [203Pb]VMT01 and undergo SPECT/CT imaging first. Later, participants in this arm will receive [68Ga]VMT02 and undergo PET/CT imaging.	Drug: [203Pb]VMT01; Diagnostic imaging radiopharmaceutical; by intravenous infusion; Drug: [68Ga]VMT02; Diagnostic imaging radiopharmaceutical; by intravenous infusion
Active Comparator: [68Ga]VMT02 first Participants randomized to this arm will receive imaging agent [68Ga]VMT02 and undergo PET/CT imaging first. Later, participants in this arm will receive [203Pb]VMT01 and undergo SPECT/CT imaging.	Drug: [203Pb]VMT01; Diagnostic imaging radiopharmaceutical; by intravenous infusion; Drug: [68Ga]VMT02; Diagnostic imaging radiopharmaceutical; by intravenous infusion

Outcome Measures

Primary Outcome Measures

1. Number of Participants with Study Imaging Agent-Associated Adverse Events (AE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. [Visit 1 (Day 1) through Visit 5 (approximately Day 60 but could extend up to Day 108); ongoing Serious Adverse Events (SAE) will be followed for no longer than Day 65 or 30 days from the date of the SAE report (whichever is later).]

   Adverse Events (AEs) will be assessed for severity according to CTCAE v5.0 and for relatedness to each of the investigative imaging agents ([203Pb]VMT01 and [68Ga]VMT02). Assessments attributed as possibly, probably, or definitely related to the imaging agent will be considered related.

2. Biodistribution of [68Ga]VMT02 [12 hours]

   Biodistribution will be calculated by utilizing PET/CT scans.

3. Biodistribution of [203Pb]VMT01 [24 hours]

   Biodistribution will be calculated by utilizing SPECT/CT scans.

4. Peak Plasma Concentration (Cmax) of [203Pb]VMT01 [24 hours]

   Cmax will be determined by blood sampling and direct radioactivity measurements.

5. Area Under the Plasma Concentration Versus Time Curve (AUC) for [203Pb]VMT01 [24 hours]

   AUC will be determined by blood sampling and direct radioactivity measurements.

6. Renal Excretion of [203Pb]VMT01 [24 hours]

   Renal excretion will be determined by urine sampling and direct radioactivity measurements.

7. Modeling of [203Pb]VMT01 Dosimetry [24 hours]

   Dosimetry will be modeled by utilizing the SPECT/CT scans.

Secondary Outcome Measures

1. MC1R Expression Correlation Between Archived Tumor Tissue and Study Imaging [Historical tissue sample (collected <365 days before study enrollment) compared to Visit 1 (Day 1) and Visit 3 (Day 21-34) imaging]

   Archived (previously collected) tumor tissue will be tested for MC1R expression and compared to study images obtained using MC1R targeted imaging agents, [203Pb]VMT01 and [68Ga]VMT02. The data will be assessed for an association between positive tissue and positive images.

2. Cancer Site Correlation Between Standard of Care Imaging Compared to Study Imaging [Historical imaging information compared to Visit 1 (Day 1) and Visit 3 (Day 21-34) imaging]

   Sites of cancer detected previously by imaging will be compared to the presence or absence of positive imaging scans with the study agents, [203Pb]VMT01 and [68Ga]VMT02.

3. Dosimetry will be Calculated for each Study Imaging Agent by Measuring the Cumulative Absorbed Dose of Radiation to the Participant's Individual Organs and Tumors [Visit 1 (Day 1) and Visit 3 (Day 21-34) imaging]

   For a given participant, dosimetry calculations will be compared between the two imaging agents with respect to cumulative absorbed dose of radiation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 89 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Diagnosed with Stage IV metastatic melanoma, or inoperable Stage III equivalent

2. Baseline fluorodeoxyglucose (FDG)-PET scan available from within 30 days prior to date of enrollment

3. Blood counts and metabolic results within protocol limits within 14 days prior to enrollment

4. Ability to lie flat and still for a minimum of two hours for imaging

5. Male and female participants with reproductive potential must agree to use highly effective contraception in preparation of the study, during the study, and for 4 weeks following the last dose of an investigative imaging agent

6. Documented life expectancy of at least 3 months

Exclusion Criteria:

1. Active secondary malignancy

2. Prior treatment (for any reason) with radioactive nuclides; imaging tracers are acceptable

3. Pregnancy or breast feeding a child

4. Uncontrolled infection

5. Treatment with another investigational drug within 30 days prior to enrollment date

6. Any treatment with BRAF inhibitors since the baseline FDG-PET scan or plans for such treatment during the study

7. Kidney function not within protocol limits

8. BMI>40 kg/m2

9. History of a condition resulting in anaphylaxis or angioedema

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Viewpoint Molecular Targeting
• Mayo Clinic

Investigators

• Principal Investigator: Frances L Johnson, MD, Viewpoint Molecular Targeting
• Principal Investigator: Geoffrey B Johnson, MD, PhD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Viewpoint Molecular Targeting
• ClinicalTrials.gov Identifier: NCT04904120
• Other Study ID Numbers: TIMAR1
• First Posted: May 27, 2021
• Last Update Posted: Aug 10, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Viewpoint Molecular Targeting: Melanoma; Theranostic; Radiopharmaceutical; Radiotherapy; Alpha-Particle; Diagnostic; Metastatic; Single Photon Emission Computed Tomography (SPECT); Positron Emission Tomography (PET); Melanocortin Receptor Sub-type 1 (MC1R); VMT01; VMT02; Pb-203; Ga-68; Cancer; Immunohistochemistry (IHC)
• Additional relevant MeSH terms: Melanoma

Study Results

No Results Posted as of Aug 10, 2022